Donald Y.M. Leung, MD, PhD Journal of Allergy and Clinical Immunology

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Presentation transcript:

Atopic dermatitis: New insights and opportunities for therapeutic intervention Donald Y.M. Leung, MD, PhD Journal of Allergy and Clinical Immunology Volume 105, Issue 5, Pages 860-876 (May 2000) DOI: 10.1067/mai.2000.106484 Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 1 Immunologic pathways involved in the progression of AD. These patients have a systemic T helper type 2 (TH2) response with elevated IgE and eosinophilia with low-level TH2 cytokine expression in uninvolved skin. The acute skin lesions are associated with marked infiltration of TH2 cells. However, with the infiltration of eosinophils and macrophages in chronic AD, there is a rise in IL-12 expression and a switch to T helper type 1 (TH1) cellular responses. This biphasic switch TH2/TH1 switch in immune responses is paralleled clinically and histologically by acute papulation and spongiosis followed by development of lichenification, epidermal hyperplasia, and dermal fibrosis. LC, Langerhans cells; MC, mast cells; CLA, cutaneous lymphoid antigen. Journal of Allergy and Clinical Immunology 2000 105, 860-876DOI: (10.1067/mai.2000.106484) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 2 Immune mechanisms of staphylococcal superantigen action. Journal of Allergy and Clinical Immunology 2000 105, 860-876DOI: (10.1067/mai.2000.106484) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 3 Structures of immunosuppressive macrolides. Journal of Allergy and Clinical Immunology 2000 105, 860-876DOI: (10.1067/mai.2000.106484) Copyright © 2000 Mosby, Inc. Terms and Conditions

Fig. 4 Mechanism of immunosuppressive macrolide action in T cells. Antigen-mediated stimulation of the T cell receptor (TCR) leads to phospholipase C–mediated generation of diacylglycerol and inositol triphosphate (IP 3), activation of protein kinase C, an increase in cytosolic calcium, formation of an activated calmodulin-calcineurin complex, and formation of nuclear factor of activated T cells (NF-ATc) required for transcription of the IL-2 gene. Cyclosporin A, tacrolimus, and ascomycins bind to their respective immunophilins to inhibit the phosphatase action of calcineurin and block nuclear translocation of the cytoplasmic subunit of the nuclear factor of activated T cells transcription factor. Journal of Allergy and Clinical Immunology 2000 105, 860-876DOI: (10.1067/mai.2000.106484) Copyright © 2000 Mosby, Inc. Terms and Conditions